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Biomedical subjects

Leonardo Pantoni

Publications and source records attributed to Leonardo Pantoni.

At least 19 recordsLinked to original sources
PubMed2007

Risk of rapid global functional decline in elderly patients with severe cerebral age-related white matter changes: the LADIS study.

BACKGROUND: Age-related white matter changes (ARWMCs), frequently detected on neuroimaging, are associated with motor, cognitive, urinary, and mood disorders. The LADIS (LeukoAraiosis and DISability) Study primarily aims to assess ARWMCs as a determinant of global functional decline in the elderly population. METHODS: We enrolled 639 patients (mean age, 74.1 +/- 5.0 years; 45.1% male) referred for nondisabling complaints, who had ARWMCs detected on brain magnetic resonance imaging (MRI) of mild, moderate, or severe grade according to the Fazekas scale. At the 1-year follow-up, 619 were reassessed using the Instrumental Activities of Daily Living (IADL) scale. Of these, 506 were totally independent at baseline, and 113 were impaired in only 1 item of the IADL scale. We studied the 1-year transition to 2 or more activities limited and selective functional impairments as cofactors of functional decline. RESULTS: The rate of transition was 9%, 15%, and 26%, in the mild, moderate, and severe ARWMC group, respectively. Comparing the severe with the mild ARWMC groups and adjusting for age and for other predictors of decline, the risk was more than 2-fold higher (odds ratio; 2.38; 95% confidence interval, 1.29-4.38) in patients with 0 or 1 activity limited, and 3-fold higher (odds ratio, 3.02; 95% confidence interval, 1.34-6.78) among patients fully independent at baseline. Both motor and cognitive deterioration predominantly explained the effect of ARWMCs on global functional decline. CONCLUSION: Elderly patients who are functionally independent and who have severe ARWMCs are at considerable risk of becoming more dependent in a short period, mostly owing to motor and cognitive deterioration.

Aged↗
PubMed2006

Corpus callosum atrophy is associated with mental slowing and executive deficits in subjects with age-related white matter hyperintensities: the LADIS Study.

BACKGROUND: Previous research has indicated that corpus callosum atrophy is associated with global cognitive decline in neurodegenerative diseases, but few studies have investigated specific cognitive functions. OBJECTIVE: To investigate the role of regional corpus callosum atrophy in mental speed, attention and executive functions in subjects with age-related white matter hyperintensities (WMH). METHODS: In the Leukoaraiosis and Disability Study, 567 subjects with age-related WMH were examined with a detailed neuropsychological assessment and quantitative magnetic resonance imaging. The relationships of the total corpus callosum area and its subregions with cognitive performance were analysed using multiple linear regression, controlling for volume of WMH and other confounding factors. RESULTS: Atrophy of the total corpus callosum area was associated with poor performance in tests assessing speed of mental processing--namely, trail making A and Stroop test parts I and II. Anterior, but not posterior, corpus callosum atrophy was associated with deficits of attention and executive functions as reflected by the symbol digit modalities and digit cancellation tests, as well as by the subtraction scores in the trail making and Stroop tests. Furthermore, semantic verbal fluency was related to the total corpus callosum area and the isthmus subregion. CONCLUSIONS: Corpus callosum atrophy seems to contribute to cognitive decline independently of age, education, coexisting WMH and stroke. Anterior corpus callosum atrophy is related to the frontal-lobe-mediated executive functions and attention, whereas overall corpus callosum atrophy is associated with the slowing of processing speed.

Aged↗
PubMed2006

Midlife respiratory function related to white matter lesions and lacunar infarcts in late life: the Prospective Population Study of Women in Gothenburg, Sweden.

BACKGROUND AND PURPOSE: Increased evidence suggests that poor respiratory function increases risk of ischemic damage to the brain. Longitudinal studies on respiratory function and cerebral small-vessel disease are lacking. We examined midlife and late-life respiratory function in relation to small-vessel disease on computed tomography (CT) in women followed for 26 years. METHODS: White matter lesions (WMLs) and lacunar infarcts were rated on brain CT scans in 2000 in 379 women 70 to 92 years of age from a longitudinal population study in Göteborg, Sweden. Respiratory function was measured by peak expiratory flow (PEF) in 1974 and 2000 and by forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) in 1980 and 2000. RESULTS: Lower FVC and FEV1 in 1980 and 2000 were associated with presence and severity of WMLs and lacunar infarcts in 2000. Per 1-SD decrease of FVC in 1980, odds ratios (95% CIs) were 1.49 (1.11 to 2.02) for presence of WMLs and 1.95 (1.34 to 2.84) for lacunar infarcts after adjustment for potential confounders. Per 1-SD decrease of FEV1 in 1980, adjusted odds ratios were 1.46 (1.06 to 2.00) for presence of WMLs and 1.42 (1.02 to 1.97) for lacunar infarcts. PEF in 1974 and 2000 was not associated with WMLs or lacunar infarcts. CONCLUSIONS: WMLs and lacunar infarcts in elderly women were related to lower midlife respiratory function. Although our data may not establish causation between lower respiratory function and small-vessel disease, they imply the importance of good respiratory function in midlife.

Brain↗
PubMed2006

Postmortem examination of vascular lesions in cognitive impairment: a survey among neuropathological services.

BACKGROUND AND PURPOSE: A full appreciation of the presence of cerebral vascular lesions in cognitively impaired patients can be ultimately reached at the neuropathological level. However, there are no detailed guidelines regarding what neuropathologists should look for at autopsy in cases of suspected vascular dementia or vascular cognitive impairment. We aimed at surveying the postmortem neuropathological procedures used in different centers in examining brain lesions of presumable or possible vascular origin in cognitively impaired patients. METHODS: Thirteen laboratories participated in the survey by filling in a semistructured questionnaire. We reviewed sampling and histology procedures in use and the neuropathological definitions of some of these lesions. Neuropathological criteria for the definition of a vascular origin of the dementing process were also surveyed. RESULTS: A large variability across centers was observed in the procedures used for the neuropathological examination and the histology techniques. Heterogeneity existed also in the definition of commonly found lesions (eg, white matter alterations, small vessel disease), interpretation of whether or not the lesions were reputed to be of vascular origin, and consequently in the interpretation of the cause of cognitive decline. CONCLUSIONS: The appreciation of the presence of neuropathologically verified vascular lesions in cognitively impaired cases may be heavily influenced by the laboratory tools used and also by the heterogeneity of the criteria applied in different centers. Harmonization of neuropathological procedures is badly needed in the field of vascular dementia and vascular cognitive impairment to better understand the association between various vascular lesions and clinical symptoms such as cognitive impairment.

Artifacts↗
PubMed2006

Age, hypertension, and lacunar stroke are the major determinants of the severity of age-related white matter changes. The LADIS (Leukoaraiosis and Disability in the Elderly) Study.

BACKGROUND: Age-related white matter changes (ARWMC), seen on neuroimaging with high frequency in older people, are thought to be consequent to the effect of vascular risk factors and vascular diseases including hypertension and stroke. Among the proofs conventionally required for a factor to be considered a risk factor for a definite pathology, there is the demonstration of a trend in risk exposure related to disease severity. We sought whether such a trend existed in the association of vascular risk factors or comorbidities with the severity of ARWMC aiming particularly at further elucidating the relative roles of hypertension and stroke in this regard. METHODS: The LADIS (Leukoaraiosis and Disability) Study is evaluating the role of ARWMC as an independent determinant of the transition to disability in the elderly. Six hundred and thirty-nine nondisabled subjects (mean age 74.1+/-5.0, M/F: 288/351) with ARWMC of different severity grades on MRI (mild, moderate, or severe according to the Fazekas scale) were assessed at baseline for demographics, vascular risk factors, and comorbidities, and are being followed up for 3 years. RESULTS: Age, frequency of hypertension and history of stroke increased along with increasing ARWMC severity independently of other factors. For hypertension, however, this occurred only in subjects without a stroke history, while for stroke history, it mainly depended on lacunar stroke. The amount of cigarettes smoked and the interaction between hypercholesterolemia and smoking predicted only the most severe ARWMC grade. CONCLUSIONS: The LADIS Study confirms that age, hypertension and lacunar strokes are the major determinants of ARWMC. Smoking and hypercholesterolemia provide additional risk.

Age Factors↗
PubMed2006

Impact of white matter hyperintensities scoring method on correlations with clinical data: the LADIS study.

BACKGROUND AND PURPOSE: White matter hyperintensities (WMH) are associated with decline in cognition, gait, mood, and urinary continence. Associations may depend on the method used for measuring WMH. We investigated the ability of different WMH scoring methods to detect differences in WMH load between groups with and without symptoms. METHODS: We used data of 618 independently living elderly with WMH collected in the Leukoaraiosis And DISability (LADIS) study. Subjects with and without symptoms of depression, gait disturbances, urinary incontinence, and memory decline were compared with respect to WMH load measured qualitatively using 3 widely used visual rating scales (Fazekas, Scheltens, and Age-Related White Matter Changes scales) and quantitatively with a semiautomated volumetric technique and an automatic lesion count. Statistical significance between groups was assessed with the chi2 and Mann-Whitney tests. In addition, the punctate and confluent lesion type with comparable WMH volume were compared with respect to the clinical data using Student t test and chi2 test. Direct comparison of visual ratings with volumetry was done using curve fitting. RESULTS: Visual and volumetric assessment detected differences in WMH between groups with respect to gait disturbances and age. WMH volume measurement was more sensitive than visual scores with respect to memory symptoms. Number of lesions nor lesion type correlated with any of the clinical data. For all rating scales, a clear but nonlinear relationship was established with WMH volume. CONCLUSIONS: Visual rating scales display ceiling effects and poor discrimination of absolute lesion volumes. Consequently, they may be less sensitive in differentiating clinical groups.

Aged↗
PubMed2006

Relationship between periventricular and deep white matter lesions and depressive symptoms in older people. The LADIS Study.

BACKGROUND: Both types of cerebral white matter hyperintensities, periventricular (PVL) and deep white matter lesions (DWML) have been previously associated with the development of depression in older subjects. However, it remains controversial as to whether PVL, DWML, or both are most strongly associated with depression and this was the aim of the current study. METHODS: In a pan-European multicentre study of 626 older subjects, we examined the relationship between PVL and DWML, depressive symptoms (GDS quintile), cognitive status (MMSE), hypertension and history of stroke. RESULTS: In univariate analysis we found that depressive symptoms as assessed by GDS were associated with both types of white matter lesions (Spearman rho = 0.12 p = 0.002 for DWML and rho = 0.09 p = 0.01 for PVL). Using ordinal logistic regression analysis the total DWML score (p = 0.041), rather than PVL (p = 0.9) was found to predict GDS scores. CONCLUSIONS: DWML, but not PVL, were most strongly associated with depressive symptoms in this sample. As DWML (unlike PVL) are associated with vascular ischaemic damage, our findings are consistent with the 'vascular depression' hypothesis. Longitudinal studies are needed to clarify the time course of these relationships, in particular, whether modifying DWML alters the natural history of depression.

Age of Onset↗
PubMed2006

White matter hyperintensities rather than lacunar infarcts are associated with depressive symptoms in older people: the LADIS study.

OBJECTIVE: Both white matter hyperintensities (WMH) and lacunar infarcts have been associated with the development of depression in older subjects, although the relative importance of the two and the influence of lesion location and concomitant vascular disease are unclear. This study investigates the relationship between location and burden of WMH and lacunes on depressive features in older people. METHOD: In a pan-European multicenter study of 626 older subjects, the authors examined the relationship between regional magnetic resonance imaging white matter hyperintensities, number of lacunar infarcts, depressive symptoms as assessed by the 15-item geriatric depression scale (GDS), cognitive status (Mini-Mental Status Examination), hypertension, and self-perceived health quality of life (QoL). RESULTS: The authors found depressive symptoms to be correlated with WMH rating in the frontal (N=626; Spearman's rho=0.161, p <0.001) and temporal (rho=0.14, p <0.001) but not occipitoparietal region (rho=0.07, p=0.07). Basal ganglia lacunes were only weakly correlated with GDS (rho=0.09, p=0.03), and lacunes in other regions showed no association. In a ordinal logistic regression model (controlling for QoL, Mini-Mental Status Examination, age, and with an interaction between WMH and hypertension), temporal WMH in the absence of hypertension independently predicted GDS, whereas neither history of stroke nor number of lacunar infarcts did. The authors compared left- versus right-sided WMH and found no effect of laterality on depressive symptoms. CONCLUSIONS: The results suggest that in this population of nondisabled older people, WMH have a greater influence on depressive symptoms than infarcts.

Aged↗
PubMed2006

Leukoaraiosis predicts hidden global functioning impairment in nondisabled older people: the LADIS (Leukoaraiosis and Disability in the Elderly) Study.

OBJECTIVES: To determine whether leukoaraiosis severity is independently associated with differences in global functioning in nondisabled elderly patients. DESIGN: Cross-sectional data analysis from an ongoing longitudinal multicenter and multinational study. SETTING: The Leukoaraiosis and Disability Study, a collaboration aimed at assessing leukoaraiosis as an independent predictor of the transition to disability in older people. PARTICIPANTS: Six hundred thirty-nine nondisabled subjects (288 men, 351 women, mean age+/-standard deviation 74.1+/-5.0) with magnetic resonance imaging-detected leukoaraiosis of different severity and presenting with one of the following: mild cognitive or motor disturbances, minor cerebrovascular events, or mood alterations or in whom leukoaraiosis was incidentally identified. MEASUREMENTS: Centralized assessment of leukoaraiosis severity according to the three severity degrees of the Fazekas scale; Disability Assessment for Dementia (DAD) Scale for measurement of global functioning. RESULTS: At baseline, 44% of participants had a mild, 31% a moderate, and 25% a severe degree of leukoaraiosis. A significant trend toward declining performance on the DAD Scale was apparent with increasing leukoaraiosis score severity (total score=98.8, 98.6, 97.5, respectively, in the three leukoaraiosis categories, analysis of variance P=.002). Similar trends were obtained for basic (P=.01) and instrumental (P<.001) function items. The statistical significance of these differences was confirmed in a multiple linear regression analysis correcting for numerous factors known to influence disability in older people. Executive function test performance declined along with increasing leukoaraiosis severity and was significantly related to DAD total score. CONCLUSION: Even in nondisabled elderly patients, levels of functional ability are related to white matter lesion severity. Executive dysfunction may mediate this relationship.

Activities of Daily Living↗
PubMed2006

Development of a neuropsychological battery for the Leukoaraiosis and Disability in the Elderly Study (LADIS): experience and baseline data.

The relationship between age-related white matter changes and cognitive performance in independent elderly people is still not clear. The Leukoaraiosis and Disability in the Elderly study (LADIS) involves 11 European centers. It aims to assess the role of the age-related white matter changes as an independent factor in the transition to disability, and in cognitive performance of an independent elderly population. A comprehensive neuropsychological battery was constructed in order to harmonize the cognitive assessment across countries. Patients were evaluated at baseline and during the 3-year follow-up with the Mini-Mental State Examination, a modified version of the VADAS-Cog (Alzheimer's Dementia Assessment Scale plus tests of Delayed recall, Symbol digit, Digit span, Maze, Digit cancellation and Verbal fluency), Trail making and Stroop test. Six hundred thirty-eight patients (mean age 74 +/- 5 years; mean educational level 10 +/- 4, F/M: 351/287) were included in this study. Neuropsychological data were analyzed test by test and also grouped in three compound measures (executive, memory and speed/motor control domains). Older subjects (>74 years) performed significantly worse than younger subjects on the ADAS-Mod and on the tests of memory (t(631) = 3.25; p = 0.001), executive functions (t(581) = 4.68; p = 0.001) and speed/motor control (t(587) = 4.01; p = 0.001). Participants with higher educational level (>8 years of school) showed better performances on the compound measures for memory (t(631) = 3.25; p = 0.001), executive functions (t(581) = 4.68; p = 0.001) and speed/motor control (t(587) = 4.01; p = 0.001). Using multiple regression analysis models to study the influence of demographic variables on cognitive performance, age and education remained important variables influencing test performance. In the LADIS population baseline data, older age and lower educational levels negatively influence neuropsychological performance.

Aged↗
PubMed2005

Small vessel disease and general cognitive function in nondisabled elderly: the LADIS study.

BACKGROUND AND PURPOSE: On cerebral magnetic resonance imaging (MRI), white matter hyperintensities (WMH) and lacunes are generally viewed as evidence of small vessel disease. The clinical significance of small vessel disease in terms of global cognitive function has as yet not been completely clarified. We investigated the independent contribution of WMH and lacunes to general cognitive function in a group of independently living elderly with varying degrees of small vessel disease. METHODS: Data were drawn from the multicenter, multinational Leukokraurosis and Disability (LADIS) study. There were 633 independently living participants. General cognitive function was assessed using the Mini Mental State Examination (MMSE) and the modified Alzheimer Disease Assessment Scale (ADAS). On MRI, WMH was rated as mild, moderate, or severe. Lacunes were rated as none, few (1 to 3), or many (4 or more). RESULTS: In the basic analysis, increasing severity of both WMH and lacunes was related to deteriorating score on the MMSE and ADAS. When WMH and lacunes were entered simultaneously, both MRI measures remained significantly associated with MMSE score. Increasing severity of WMH remained associated with ADAS score, whereas the association with lacunes became less prominent. These associations were independent of other risk factors for dementia, like education, depression, vascular risk factors, or stroke. CONCLUSIONS: We found WMH and lacunes to be independently associated with general cognitive function in a sample of independently living elderly. These results highlight the fact that WMH and lacunes should both be evaluated when assessing small vessel disease in relation to cognitive function.

Aged↗
PubMed2005

Efficacy and safety of nimodipine in subcortical vascular dementia: a randomized placebo-controlled trial.

BACKGROUND AND PURPOSE: Evidence of drug efficacy in vascular dementia (VaD) is scanty. Therapeutic trials should address VaD subtypes. We studied the efficacy and safety of the calcium antagonist nimodipine in subcortical VaD. METHODS: 242 patients defined as affected by subcortical VaD based on clinical (ICD-10) and computed tomography criteria were randomized to oral nimodipine 90 mg/d or placebo. RESULTS: 230 patients (121 nimodipine, mean age 75.2+/-6.1; 109 placebo, 75.4+/-6.0) were valid for the intention-to-treat analysis. At 52 weeks, the Sandoz Clinical Assessment Geriatric scale 5-point variation (primary outcome measure) did not differ significantly between the 2 groups. However, patients on nimodipine performed better than placebo patients in lexical production (P<0.01) and less frequently showed deterioration (3 or more point-drop versus baseline) on a Mini-Mental State Examination (28.1% versus 50.5%; chi2 P<0.01) and Global Deterioration Scale (P<0.05). Dropouts and adverse events were all significantly more common among placebo than nimodipine patients, particularly cardiovascular (30 versus 13; RR, 2.26; 95% CI, 1.11 to 4.60) and cerebrovascular events (28 versus 10; RR, 2.48; 95% CI, 1.23 to 4.98), and behavioral disturbances requiring intervention (22 versus 5; RR, 3.88; 95% CI, 1.49 to 10.12). A worst-rank analysis, performed to correct for the effect of the high dropout rate in the placebo group, showed additional significant differences in favor of nimodipine in Set Test and MMSE total scores. CONCLUSIONS: Nimodipine may be of some benefit in subcortical VaD. Confirming previous results, the safety analysis of this study shows that in this high-risk population, nimodipine might protect against cardiovascular comorbidities.

Aged↗
PubMed2005

White matter hyperintensities and depression--preliminary results from the LADIS study.

BACKGROUND: White matter hyperintensities have been associated with the development of depression in older subjects, though the details of this relationship are not fully understood. METHODS: In a pan-European multicentre study of 629 older subjects, we examined the relationship between MRI white matter hyperintensities (WMH), depressive symptoms and self perceived health quality of life (QOL). WMH were rated using a three-point scale. RESULTS: We found depressive symptoms as assessed by the geriatric depression 15-item scale to be associated with WMH rating (Spearman's rho 0.11, p = 0.008) and also with the Euro-QOL health score (Spearman's rho -0.5, p < 0.001). In a ordinal logistic regression model, QOL was found to strongly predict GDS score (p < 0.001) and severe vs mild WMH were associated with increased depression (p = 0.028). The relationship between history of severe depression and WMH score was examined, but there were no differences either between those with and without a history of severe depression, or those with an early vs late onset of depression. CONCLUSIONS: The results suggest that WMH play a role in increasing depressive symptoms, even when perceived quality of life is controlled for as a possible mediating factor.

Aged↗
PubMed2005

Impact of age-related cerebral white matter changes on the transition to disability -- the LADIS study: rationale, design and methodology.

Age-related white matter changes (ARWMC) on brain MRI have been associated with cognitive, motor, mood and urinary disturbances. These factors are known to contribute to disability in elderly people, but the impact of ARWMC and of their progression on the transition to disability is not determined. The LADIS (Leukoaraiosis and Disability in the Elderly) study aims at assessing the role of ARWMC as an independent predictor of the transition to disability in initially nondisabled elderly (65-84 years). Subjects who are not impaired or impaired on only 1 item of the Instrumental Activity of Daily Living (IADL) scale, presenting with different grades of ARWMC severity, were enrolled. Eleven European centers are involved. All the patients were assessed at baseline using an extensive set of clinical and functional tests including global functioning, cognitive, motor, psychiatric and quality of life measures. MRI studies were performed at baseline and will be repeated at the end of the follow-up period to evaluate changes of ARWMC and other lesions. ARWMC were categorized into mild, moderate or severe using the scale of Fazekas et al. For each ARWMC severity class, the primary study outcome is the transition to disability defined as an impairment on 2 or more IADL scale items. Secondary outcomes are the occurrence of dementia, depression, vascular events or death. Six-hundred and thirty-nine subjects (mean age 74.13 +/- 5.0 years, M/F: 288/351) were enrolled in a hospital-based setting and are being followed up for up to 3 years. The large and comprehensive set of measures in LADIS enables a comprehensive description of their functional and clinical features to be examined in relation to different morphological patterns and severity of ARWMC. The longitudinal design will give insight into the possible role of ARWMC and their progression as an independent contributor to disability in the elderly, eventually helping to develop preventive strategies to reduce the burden of disability in late life. The study results may also help to standardize, on an international basis, tools and criteria to identify early stages of disability.

Activities of Daily Living↗
PubMed2004

Treatment of vascular dementia: evidence from trials with non-cholinergic drugs.

A considerable number of therapeutic trials have been performed in vascular dementia (VaD). The results of these trials have generally been considered as disappointing and no drug treatment has been so far approved for the treatment of VaD by regulatory agencies. The aim of the present paper is to critically review the results of randomized clinical trials performed with non-cholinergic drugs in VaD. The conclusions of the present review are that: (1) some drugs such as nicergoline, memantine, posatirelin, propentofylline, and pentoxifylline have shown some, although partly limited, benefits in VaD patients; (2) besides a lack of efficacy of the tested drugs, possible causes of the negative results of many randomized clinical trials in VaD are the enrollment of patients with heterogeneous subtypes of VaD, the small sample size, and the use of end-points and cognitive tests inadequate for the VaD setting because derived from previous experience in the field of Alzheimer disease. Preliminary analyses show that focusing therapeutic trials on specific forms of VaD such as the subcortical type may lead to results different from those obtained in a heterogeneous VaD group. This selective focus seems to be better suited for disclosing specific treatments in the field of VaD.

Dementia, Vascular↗